An indispensable role for the chemokine receptor CCR10 in IgA antibody-secreting cell accumulation.
The differential expression of chemokines and chemokine receptors, by tissues and leukocytes, respectively, contributes to the specific accumulation of leukocyte subsets to different tissues. CCR10/CCL28 interactions are thought to contribute to the accumulation of IgA Ab-secreting cells (ASC) to mucosal surfaces, such as the gastrointestinal tract and the lactating mammary gland. Although the role of CCL28 in lymphocyte homing is well established, direct in vivo evidence for CCR10 involvement in this process has not been previously shown. In this study, we describe the generation of a CCR10-deficient mouse model. Using this model, we demonstrate that CCR10 is critical for efficient localization and accumulation of IgA ASC to the lactating mammary gland. Surprisingly, IgA ASC accumulation to the gastrointestinal tract is minimally impacted in CCR10-deficient mice. These results provide the first direct evidence of CCR10 involvement in lymphocyte homing and accumulation in vivo, and demonstrate that reliance on CCR10-mediated recruitment of IgA ASC varies dramatically within mucosal tissues.
Morteau
Olivier
O
Perlmutter Laboratory and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Gerard
Craig
C
Lu
Bao
B
Ghiran
Sorina
S
Rits
Miriam
M
Fujiwara
Yuko
Y
Law
Yuetching
Y
Distelhorst
Kathryn
K
Nielsen
Elizabeth M
EM
Hill
Erica D
ED
Kwan
Raymond
R
Lazarus
Nicole H
NH
Butcher
Eugene C
EC
Wilson
Eric
E
D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000378:metabolism*; D007420:Intestine, Large / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007774:Lactation / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008321:Mammary Glands, Animal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054447:Receptors, CCR10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C515707:Ccr10 protein, mouse; D007070:Immunoglobulin A; D054447:Receptors, CCR10